Hyperlipidemia Flashcards
What organ produces most of the body’s cholesterol (where does the rest come from)
The Liver (75-80%), the rest from the diet
Stats about Hyperlipidemia?
1:6 Americans have high cholesterol
1:3 of those are treated and in good control
Less than have of those diagnosed with high cholesterol are receiving treatment
What is dyslipidemia?
The elevation of plasma cholesterol, triglycerides or both or an elevation of a low density lipoprotein level (LDL)
3 Types of triglycerides
1) Saturated - Has greatest impact on increasing LDL (all carbons fully saturated with hydrogens). (from Meat, dairy, and exotic oils
2) Monosaturated - OK in moderation from vegetable oils, peanuts and avocados.
3) Polyunsaturated - Best for you, only essential fats.. from Sunflower, safflower oils and cold water fish
_______ carries 60-70% of total serum cholesterol
LDL
Mono and Polyunsaturated triglycerides are only good for you in what conditions
Liquid form and at room temperature
The higher the density of cholesterol ______
The lower the lipid content
What is a lipoprotein comprised of?
A lipid and an apoprotein
What is the rate limiting step in the cholesterol synthesis process
The enzyme HMG CoA reductase
Classifications of Hyperlipidemia/Dyslipidemia
Primary and Secondary
Increase in cholesterol, Triglycerides or both
What is Primary Hyperlipidemia?
A single or multiple genetic mutation that results in the overproduction or defective clearance of cholesterol usually due to a defect in an apoprotein.
What are the 3 types of Primary Hyperlipidemia
1) Familial hypercholesterolemia - An increase in LDL
2) Familial combined hyperlipidemia - An increase in both LDL and VLDL
3) Familial hypertriglyceridemia - An increase in triglycerides (usually autosomal dominant)
What is the big dangers of familial hypertriglyceridemia?
50% of these patients have an MI under age 60
More at risk for pancreatitis
What to do if diagnosed with primary hyperlipidemia
Test all family members
What are the lab findings of Type IIa Hypercholesteromia?
TG normal, Increase LDL and cholesterol
What is the defect found in Type IIa Hypercholesteromia?
An LDL recepotor defect
What are the clinical features of Type IIa Hypercholesteromia?
Premature vascular disease, xanthomas. Onset found at all ages. Untreated life expectancy = 20 years
What is the therapy of Type IIa Hypercholesteromia?
Low fat/low cholesterol diet, MEDS, intestinal bypass
What is secondary hyperlipidemia?
High cholesterol due to a significant secondary cause because patients tend to have an athrogenic combination of high TG, high LDL fractions or low HDL
Environmental/medical risk factors for secondary hyperlipidemia?
Sedentary lifestyle Excessive intact of bad fats and cholesterol DM or Metabolic syndrome ETOH or tobacco use Chronic Kidney disease/nephrosis Hypothyroidism Cholestatic liver disease Medications
What medications can contribute to secondary hyperlipidemia?
Thiazides/beta blockers Cyclosporine Retinoids Estrogens and progesterone Anabolic and corticosteroids Carbamazepine Protease inhibitors
Risk factors of secondary hyperlipidemia for people with Type 2 DM. (how does it happen?)
Combo of obesity, poor control or both resulting in an increase FFA.
An increase in FFA leads to an increase liver VLDL production. TG rich VLDL then transfers TG and cholesterol to LDL and HDL. That promotes formation of TG rich, small dense LDL and clearance of TG rich HDL
What is the pathology of hyperlipidemia?
Deposits of cholesterol in vascular walls creates Fatty streaks that become fibrous plaques. This creates less elasticity of the walls and a narrowing of the vessels (stenosis). Inflammation causes plaque instability leading to plaque rupture that can lead to MI, TIA and CVA
Factors to consider with hyperlipidemia when taking a patient’s history?
CV disease, Liver problems, thyroid problems, a review of medications, family history.
Factors to consider with hyperlipidemia when taking the patient’s physical exam?
Patient’s BMA, Xanthelasma’s on eyelids, Xanthomas (AT, patella, back of hand, buttocks), cream color in blood, signs of ETOH abuse, DM or Metabolic syndrome
Current labs for hyperlipidemia workup
Fasting glucose, LFT’s, Chem panel, TSH and Urine protein
What is the definition of Metabolic Syndrome?
A cluster of common conditions that increase T2DM and CVD risk.
What is the criteria for metabolic syndrome
Must have 3 of the following
- Abdominal obesity
(waist circumference >40” men, >35” women)
- Impaired glucose tolerance
(Fasting plasma glucose >100 mg/dL or on a specific
med or diagnosed with T2DM
- Low HDL
(Males 150 mg/dL or on a specific med)
- HTN
(BP >130 mmHg systolic, 85 mmHg diastolic or on
specific med)
What is the Framingham test?
Test to determine CVD risk in Asymptomatic patients within 10 years
What are the Framingham test scores
Score under 10% is low risk
Score btwn 10-20% is intermediate risk
Score 20% = High risk
Metabolic syndrome aliases
Dysmetabolic syndrome Hypertriglyceridemic waist Insulin resistance syndrome Obesity syndrome Syndrome X
What are the different guidelines of cholesterol testing
National Cholesterol Education Program (NCEP)
adults 20 or over every 5 years
US Preventative Task Force (USPSTF)
Total cholesterol and HDL every 5 years
All men over 35
Women 45 and over if @ increase for CHD
Men 20-35 and women 20-45 if increase CHD risk
What are the equations to determine lipids in the lab
1) Total cholesterol = HDL + LDL + VLDL
2) VLDL = TG/5
3) LDL = Total cholesterol - HDL - TG/5
What are the guidelines for total serum cholesterol
Under 200 -desirable
200-239 - Borderline High
240 and over - High
(Over 150 is associated with CHD risk)
What are the guidelines for serum LDL
Under 100 - optimal 100-129 - Near/above optimal 130-159 - Borderline High 160-189 - High Over 190 - Very high
What is the LDL goal for drug therapy
Try to achieve a 30-40% reduction (60% is ideal)
What are the goals for Serum HDL
Under 40 - Low
Over60 - High
What the NCEP ATP III recommendations for Framingham scores and Hyperlipidemia
Low Risk - LDL goal/initiate chng 160, drug therapy >190
Mod Risk - LDL goal/change 130, drug therapy > 160
Mod/High - LDL goal/change 130, drug therapy > 130
High Risk - LDL goal/change 100, drug therapy >100
For every ______ decrease in serum cholesterol, CV risk decreases by _____
1% decreases by 2%
Saturated fat vs. Dietary cholesterol on Serum Cholesterol
Sat. fat has much more of an influence than dietary cholesterol.
Changes in dietary cholesterol gives a modest benefit, reducing dietary saturated fats can decrease serum cholesterol by 10%
What are some dietary considerations with hyperlipidemia
1) Consume less than 10% of calories from saturated fat
2) Consume less than 300 mg/day of cholesterol
3) Keep trans fatty acid consumption low as possible
4) Emphasize fruits, vegetables and whole grains
What are some things that can raise HDL levels (and by how much)
Exercise 30 min/day - 5-20%
Weight loss - 5-10%
Modest ETOH use - 1-2 oz daily
A handful of unsalted walnuts, almonds or pecans at bedtime
Under the new guidelines what is the Framingham score that you would start treating someone for Hyperlipidemia
7.5% CVD risk in 10 years
What are the treatment goals of Hyperlipidemia/dyslipidemia?
LDL goal for low risk and no co-morbidities 20% Framingham score)
What are the 4 classes of Cholesterol meds (and 2 others)?
1) HMG CoA reductase inhibitors (STATINS)
2) Bile Acid Sequestrants
3) Fibric Acids
4) Nicotinic Acids
ALSO - Zetia (for those with Statin sensitivities and Omega 3)
What are the 1st and 2nd choices of drug therapy for Hyperlipidemia? (how much will it improve)
1st choice - Statins (HMG-CoA reductase inhibitors)
Can lower CVD risk - 20-30%
Lower LDL count - 14-63%
2nd choice - Ezetimibe (Zetia) - those with Statin intolerance
Lower LDL count - 15-20%
What do all HMG CoA reductase Inhibitor drugs end in?
-statin
What are the 6 Statin drugs?
Atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin
With is the MOA for HMG COA reductase Inhibitor (statins)?
They inhibit rate limiting enzymes in the formation of cholesterol. Give a small increase in HDL and a moderate decrease in LDL
What are the side effects of HMG COA reductase Inhibitor (statins)?
Myositis, and there are questions about them causing diabetes
What are some adverse effects of HMG COA reductase Inhibitor (statins) and what needs to be done about it?
Liver toxicity - Need to obtain LFT baseline when initiating
- Don’t need to monitor but d/c if ALT/AST is 3x
baseline
Rhabdomyolysis with acute renal failrure
- Need a baseline CPK
- Counsel patient to report any muscle pain,
tenderness. weakness or brown urine
What is the MOA of Exetimibe (Zetia)?
It blocks intestinal absorption of dietary and biliary cholesterol
What are three Bile acid-binding resins?
1) Cholestyramine
2) Colestipol
3) Colesevelam
What is the MOA of Bile acid-binding resins?
Binds bile acids in the gut and reduces enterohepatic circulation of bile acids, resulting in increased liver production of bile acids using hepatic cholesterol
What are the effects of Bile acid-binding resins?
Decreases LDL by 15-25%
No effect on HDL
20% reduction in CHD events
What is the only lipid lowering agent that is considered safe in pregnancy
Bile acid-binding resins
What are three Fibric acid derivative drugs
1) Gemfibrozil
2) Fenofibrate
3) Clofibrate
Who is Fibric acid derivative drugs most useful for and what are their MOA.
Most useful in those with high TG and low HDL
They reduce synthesis and increase breakdowns of VLDL.
How effective are Fibric acid derivative drugs?
Can reduce LDL by 10-15% and reduce TG by 40% and increase HDL by 15-20%
What is a major warning of clofibrate?
Has had an increased level of cancer in a large clinical trial
What are the sfx of Fibric acid derivative drugs?
Gallstones (cholelithiasis), hepatitis and myositis
What does Niacin do to treat Hyperlipidemia?
Reduces production of VLDL and decreases LDL by 15-25%.
It raises HDL by 25-35%
Decreases TG by 50%
Lowers Lp(a) and homocysteine levels
What are the sfx of Niacin?
Flushing. You can take an ASA prior to dosing to help prevent this
What does Omega 3 Oils do for Hyperlipidemia?
Lower triglycerides, they don’t lower mortality or risk of CV disease or events
Warnings for Omega 3 Oils
Pregnancy category C
D/C if no response after 2 months
Watch for those with fish/shellfish allergy/sensitivity
Freeze capsules if it causes GERD
Name 5 combination drug therapies for Hyperlipidemia
Statin + bile acid sequestrant
Statin + fibric acid derivative (not gemfibrozil)
Statin + niacin
Statin + fibric acid derivative (not gemfibrozil) + niacin
Statin + cholesterol absorption inhibitor
Start treating any patient (any age or healthy) when their LDL’s go above _____
190 mg/dL (start treating with a statin)
Start treating a patient with risk factors (like DM) when LDLs are ______
70 - 189 mg/dL (moderate dose of a statin). A high dose of they have above a 7.5% risk factor on Framingham scale
T/F Unexplained myalgias may occur on statins w/o CK elevation.
False, minimal but nothing requiring you to stop
Statins have drug interactions with _______
CYP3A4 inhibitors
What are examples of CYP3A4 inhibitors?
Macrolides, azole antifungals, cyclosporins, telithromycin, danazol, amiodaroine, verapamil
What is the exception of a statin that doesn’t have drug interactions with CYP3A4 inhibitors? (why?)
Pravastatin (It’s metabolized in the gut rather than the liver)
What is the Fibrate that especially interacts with statins (why?)
Gemfibrozil (inhibits metabolism, raises statin in blood and can create a toxicity)
Niacin and statins can cause ______
Myalgias
What are better medicines that should be used to lower LDL - C
1) Bile acid sequestratnts
2) Nicotinic Acid
3) Fibrates
What are better medicines that should be used to lower triglycerides?
1) Fibrates
2) Nicotinic acid
3) Omega 3 Fatty acids
What are better medicines that should be used to enhance HDL - C
1) Stains, Fibrates and Bile acids
2) Nicotinic acid
What drugs have zero affects on enhancing HDL
Ezetimibe and Omega 3’s
